The hypothesis of this work is that the expression and regulation of IgG rheumatoid factor (RF) autoantibodies rather than IgM RF is important for the pathogenesis of rheumatoid arthritis (RA). The goal of this project is to identify and characterize genes involved in the production of these autoantibodies and to determine thr molecular basis of RF reactivity. Identification of pathogenic RF in RA is critical for the design of new and more specific therapies for the treatment of RA. 1. To isolate monoclonal IgG RF-producing cells from RA synovium. 2. To clone and sequence the genes expressed in IgG RF autoantibodies and compare them to those previously described for IgM RF. 3. To determine the contribution of heavy and light chains to RF reactivity and identify individual amino acids responsible for RF binding reactivity. 4. To determine if the expression of these RF autoantibodies is related to RA disease activity by measuring RF gene expression in peripheral blood lymphocytes (PBL) and in lymphocytes from the synovium of rheumatoid arthritis patients and normal individuals.